2, 5-bis-(substituted-mercapto)-3, 4-dicyanopyrroles and their preparation



United States Patent 2,5-BIS-(SUBSTITUTED-MERCAPTO)-3,4-DICYANO- PYRROLES AND THEIR PREPARATION William I. Middleton, Claymont, Del., assignor to E. I. du Pont de Nemours and Company, Wilmington, Del., a corporation of Delaware No Drawing. Application April 20, 1955, Serial No. 502,715

22 Claims. (Cl. 260-4265) This invention relates to new substituted pyrroles and to their preparation. More particularly this invention relates to new substituted pyrroles which have attached to the carbon atoms of the pyrrole nucleus a plurality of cyano groups and a plurality of organic substituted mercapto groups or the corresponding sulfoxide or sulfone groups.

Pyrrole is a five-membered nitrogen-containing heterocyclic compound which contains two nuclear carbon-tocarbon unsaturations. The compound has somewhat unexpected properties in that it and its unsaturation resemble that of benzenoid compounds in many respects. The pyrrole nucleus occurs in natural products such as in the porphyrins of chlorophyll and hemoglobin. Although pyrroles have interesting properties, investigations heretofore have been primarily directed to pyrroles having carboxylic acid and hydrocarbon groups attached to nuclear carbons.

It is an object of this invention to provide new substituted pyrroles and a process for their preparation. A further object is to provide new substituted pyrroles which have attached to the carbon atoms of the pyrrole nucleus a plurality of cyano groups and a plurality of organic substituted mercapto groups or the corresponding sulfoxide or sulfone groups. A still further object is to provide novel substituted pyrroles from selected substituted butadienes. Other objects will appear hereinafter.

These and other objects of this invention are obtained by providing substituted pyrroles in which each of the nuclear carbon atoms bonded to nuclear nitrogen bears an group wherein R is an organic radical of up to carbons bonded to sulfur by aliphatic carbon and n is a cardinal number of 0 to 2, and each of the remaining carbon atoms of the pyrrole nucleus bears a cyano group. The new compounds of this invention are pyrroles which have no hydrogen on nuclear carbon. They have two cyano groups and two SR groups wherein the sulfur is directly attached to the nuclear carbon atoms which are attached to nuclear nitrogen of the pyrrole ring. The sulfur of the SR groups can have optionally attached to it up to two oxygen atoms. Thus, the

group designates the substituted mercapto group and the corresponding sulfoxide and sulfone. R can be any organic radical of up to 10 carbons providing it is attached to sulfur by an aliphatic carbon. Suitable radicals include hydrocarbon such as benzyl and vinyl, alkyl, hydroxyalkyl, haloalkyl, chloroalkyl, cyanoalkyl and pyridiliurn-alkyl radicals. The group SR is any organic substituted-mercapto (organic thio) group of up to 10 carbons in which the radical R is attached to sulfur by aliphatic carbon. Suitable --SR groupings include hydrocarbonmercapto (hydrocarbonthio), such as alkyl- Patented May 21, 1957 mercapto (alkylthio), benzylrnercapto (benzylthio), and vinylmercapto (vinylthio); hydroxyalkylmercapto (hydroxyalkylthio); haloalkylmercapto (haloalkylthio), such as chloroalkylmercapto (chloroalkylthio); cyanoalkylmercapto (cyanoalkylthio); and pyridilium-alkylmercapto (pyridilium-alkyl).

The new pyrroles of this invention have substituents on all of the nuclear carbons and have the structural formula wherein n is a cardinal number of 0 to 2, and R is an organic radical of up to 10 carbons, preferably of not more than 7 carbons, attached to sulfur by an aliphatic carbon and preferably by a methylene, CH2, group. The radical R includes hydrocarbons which are bonded to sulfur by aliphatic carbon, such as benzyl, vinyl and alkyl radicals. The lower (one to live carbon) alkyls, such as methyl, propyl and amyl are a particularly preferred class. Aliphatic radicals which contain elements including oxygen, nitrogen and halogen are also useful. Examples of such radicals are furfuryl, beta-hydroxyethyl, beta-chloroethyl, beta-cyanoethyl and beta-pyridiliumethyl groups.

The new substituted pyrroles of this invention are obtained by contacting an aqueous solution of a strong mineral acid with a substituted butadiene in which each of the central carbon atoms of the butadiene nucleus bears a cyano group and each of the terminal carbon atoms of the butadiene nucleus bears an amino group and an' organic substituted mercapto group of not more than 10 carbon atoms in which the organic group is bonded to sulfur by aliphatic carbon. When an oxidizing agent, such as hydrogen peroxide, is present in this reaction, sulfur undergoes oxidation to give the corresponding sulfoxy or sulfone derivatives.

These substituted butadienes which are employed to give the disubstituted mercaptopyrroles of this invention are 1,4 diamino 2,3 dicyano-l,4,-bis(substituted-mercapto)butadienes having the general formula where R is an organic radical of up to 10 carbon atoms, and preferably of not more than 7 carbon atoms, bonded by aliphatic carbon to the sulfur atom. R in these substituted butadienes and in the new pyrroles of this invention can be hydrocarbon groups which are bonded to sulfur by aliphatic carbon, such as benzyl, vinyl or alkyl, particularly the lower alkyls, e. g., methyl, ethyl, propyl, butyl or amyl. R can also be an aliphatic radical that contains substituents which include oxygen, nitrogen or halogen, e. g., as' in haloalkyl or chloroalkyl, such as betachloroethyl; hydroxyalkyl, such as beta-hydroxyethyl; and cyanoalkyl, such as beta-cyanoethyl.

The new pyrroles within the scope of this invention are obtained by the decomposition in the presence of strong mineral acid, of the l,4-diarnino-2,3-dicyano-l,4-his (substituted-mercapto)butadienes defined above. The pyrroles thus obtained have an acidic hydrogen on the nuclear pyrrole nitrogen. This can be converted to a salt group by treatment with a base and alkylated by suitable alkylating reagents.

The following examples in which the parts are by weight illustrate the preparation and properties of new compositionswithin the scope of this invention.

3 EXAMPLE I 2,5-bis(methylmercapto)-3,4-dicyanpyrrole CN CN A mixture of 100 parts of water, 56 parts of 36% hydrochloric acid, 120 parts of ethanol, and 17 parts of 1,4- diamino 1,4 bis(methylmercapto)-2,3-dicyanobutadiene was heated under reflux with stirring until all solid material had gone into solution. This required about 30 minutes. The solution was cooled, and a white crystalline precipitate formed. The precipitate was collected on a filter and washed with water. Water was added to the filtrate, and an additional amount of precipitate formed. This precipitate was also collected, combined with the first precipitate, and recrystallized from ethyl alcohol. There was obtained 13 parts of 2,5-bis(methylmercapto)- 3,4-dicyanopyrrole in the form of long white needles, M. P. 224-225 C.

Analysis.--Calcd. for CaNsI-IrSa: C, 45.91; H, 3.37; N, 20.08; 8, 30.64. Found: C, 46.04; H, 3.44; N, 20.40; S, 30.24.

EXAMPLE Il 2,5 -b is ethylm ercap to) 3,4-d icyanopyrrole CN CN NC 0N aims] [80:35 N

NE. NE:

A mixture of 0.5 part of 1,4-diamino-1,4-bis-(ethylmercapto)2,3-dicyanobutadiene and 11 parts of hydrochloric acid was heated to boiling for 5 minutes, and 4 parts of alcohol was then added. The heating was continued until all of the solid had gone into solution. The solution was cooled, and the white crystals which separated were collected on a filter, washed with water, and recrystallized from alcohol-water. There was obtained 0.3 part of 2,5-bis(ethylmercapto)-3,4-dicyanopyrrole in the form of white plates, M. P. 140-141 C.

Analysis.Calcd. for CwHuNsSa: C, 50.60; H, 4.67; N, 17.71; S, 27.02. Found: C, 50.97; H, 4.33; N, 17.62; S, 27.38.

EXAMPLE III 2,5 -b|'s( beta-hydroxye thylmercapto) -3,4-dicyanopyrrole NH; H;

NC CN HO OHICHsSllSCHsC HIGH 36% HCl 4 EXAMPLE IV 2,5 -bis( beta-chloroethylsulfonyl -3,4-dicyanopyrr0le and its salts PART A. PREPARATION FROM 1,4-DIAMINO-2,3-DI- CYANO 1.4 BIS(BETA HYDROXYETHYLMERCAPTO) BUTADIENE NO (3N ClCHzCHISOI] N [8010111011 01 One hundred parts of 1,4-diamino-2,3-dicyano-1,4-bis (beta-hydroxyethylmercapto)butadiene was slowly added to a stirred solution of 1200 parts of 36% hydrochloric acid. When all of the solid had dissolved, the solution was cooled to 0 C. and about 300 parts of 30% hydrogen peroxide was added dropwise at such a rate that the temperature did not rise above 5 C. When the addition was completed, the solution was stirred for 3 hours longer at ice-bath temperature and then allowed to slowly warm to room temperature. The white solid parts, 65% yield) which formed was collected on a filter, washed with water, and recrystallized from water. There was obtained 65 parts of 2,5-bis-(beta-chloroethylsulfonyl)-3,4- dicyanopyrrole in the form of white needles, M. P. 210212 C.

PART B. PREPARATION OF 2,5-BIS(BETA-CHLO'RO- ETHYLSULFONYL)-3,4-DICYA.NOPYRROLE FROM 3,4- DICYANO 2,5 BIS(BETA-HYDROXYETHYLTHIO)PYR- ROLE NC CN H D: HOCHaCHzS SCHzCHzOH -9 III HCl 11 NC -ON ClCHqCHrSOz N -50zCH2CHzCl The same compound was alternately prepared by oxidation of the pyrrole of Example Ill according to the following process:

A solution of 4.25 parts of 3,4-dicyauo-2,5-bis(beta-hydroxyethylmercapto)pyrrole in 60 parts of 36% hydrochloric acid was cooled at 0 C., and about 25 parts of 30% hydrogen peroxide was added dropwise to the stirred solution at such a rate that the temperature was kept below 10 C. at all time. After the addition, the solution was stirred for 2 hours at ice-bath temperature and then allowed to slowly warm to room temperature. The white solid (4.0 parts, 69% yield) which formed was collected on a filter, washed with water, and recrystallized from water. 2,5 -bis beta-chloroethylsulfonyl) -3 ,4-dicyanopyrrole was obtained in the form of white needles, M. P. 210-2l2 C.

Analysis.Calcd. for C1uHsNsS2Cl2O4; C, 32.44; H. 2.45; N, 11.35; S, 17.32; Cl, 19.15. Found: C, 32.55; H, 2.64; N, 11.38; S, 17.40; Cl, 19.26; pKa, 2.6.

PART C.-PREPARATION OF TETRAMETHYLAMMONIUM SALT 0F 2,5-BIS BETA-CHLOROETHYLSULFONYL) 3,4-DICYANOPYBROLE The filtrate from the recrystallization of this product was mixed with a solution of 5 parts of tetramethylammonium chloride in 10 parts of water. The white precipitate which formed was collected on a filter, washed with water, and recrystallized from water. There was obtained 0.34 part of the tetramethylammonium salt of 2,5-bis- (beta-chloroethylsultonyl)-3,4-dicyanopyrrole in the form of long white needles, M. P. 185-186 C. Acidic pyrroles trations are 10 to 40% of acid in water. Non-reactive of the above type form crystalline derivatives of amines water-soluble organic solvents such as alcohol can be analogous to those formed by picric acid. present during the reaction. Such solvents facilitate the Analysis.-Calcd. for ClsH2uS2N4Cl2O4: reaction by providing a homogeneous system.

o N The 1,4-diarnino-2,3-dicyano-1,4-bis(substituted-mercapto)butadienes are obtained by the base catalyzed reolorncmso 0,011,011.01 manna action of excess lnercaptan with either tetracyanoethylene N or tetracyanoethane as disclosed and claimed in my co- C, 37.92; H, 4.55; N, 12.64; S, 14.46; Cl, 15.99. Found: pending U. S. patent application, Serial No. 491,512, filed C, 37.94; H, 4.55; N, 12.71; S, 14.66; Cl, 16.41. March 1, 1955. For example l,4-diamino-2,3-dicyano EXAMPLE V 2,5-bis(2-[I-pyridylium]ethylsulfonyl)-3.4- dicyanopyrrolide chloride dihydrate NC on o o N -CH2CH2SO w QICHzCHr- N .ZHrO Cl A solution of 5.0 parts of 2,5-bis(betachloroethylsul- 1,4-bis(beta-hydroxyethylmercapto)butadiene can be ob fonyl)-3,4-dicyanopyrrole (Example IV) in 25 parts of tained as follows:

pyridine was allowed to stand at room temperature for A uti n of 2.8 parts f tetracyanoethylene in 5 two hours and then heated under reflux for five minutes. Parts Of acetone was mixfid With a solution (If 2 Parts of The white precipitate which formed was collected on a triethylamine in about parts of beta-mercaptoethanol. filter and Washed with ether. There wa obtain d 4 5 30 The resultant solution was cooled in an ice-bath for ten parts of a white powder. This material was recrystallized minutes, and Poured into 1000 Parts of Waief- Aim! from water to give 3,7 parts f h s l standing at room temperature for about one hour, the

crystalline precipitate which formed was collected on a filter, washed with water, and dried. There was obtained cziflmNtsiotclzlm 22.5 parts (81% yield) of l,4-diamino-2,3-dicyano-1,4- bis(beta-hydroxyethylmercapto)butadiene in the form of in the form of white needles which melted first at 158- long, while, highly refractive needles, M. P. 176-177 C. 160 (3., resolidified and then remelted at 245248 c. The tetrdcya y was p p as disclosed, in

Analysis.Calcd. for C2oH22N5S20sCl: C, 45.49; H, Cairns and Graef U. S. patent application Serial No. 4.20; N, 13.27; 5. 12.14; Cl, 6.72. Found: c, 44.59; H, 382.84 fil September 9 3, y r i f s f 4.33; N, 13.16; S, 12.00; Cl, 6.70. monochloride with malononitrile as in the following In addition to the compounds described in the examples, PIOCEdUrCI the following are included in this invention: 2,5-bis(amyl- Sulfur monochloride p was added slowly mer apt 3,4 di l 2,5 bi h 1 1f ing the course of six hours to a refluxing solution of 33 yl) 3,4 dicyanopyrrole, 2,5 bi (mthy1 u1fi y1) 4- parts of nlalononitrile in about 600 parts of chloroform. dicyanopyrrole, 2,5 bis(bcnzylmercapto) 3,4 dicyano- After the mixture refluxed for an additional 20 hours, the r l ,z,5 bi f f l w 3,4.dicyanopyn'olg, chloroform was removed by heating on a steam bath. 2,5 bisweta cyanoethylmercapm) 4 dicyanopyr- The crystalline residue was extracted with diethyl ether in l d 2 5 i 1 3 4 d 1 a Soxhlet extractor. Evaporation of the ether extract The new pyrroles arc acidic due to the presence of hy- 0 gave crllde tatracyanoethylenc which was flmhel Purified drogen on the pyrrole nitrogen. They can be converted to by Sublimation at under a Pressum salts such as alkali metal or ammonium salts which have Tetraclal'loethancl which can bfi p y l Place increased Solubility in water. the tetracyanoethylene, is obtainable from the latter by The sulfoxides and sulfonyl compounds are also inreducnon, with hydrogen 3 mercapmn as cluded within the scope of this invention. These comdisclosed in Patent application Serial pounds, i. e., those of the general formula wherein n is 1 421997 fi Apnl 1954 as follows:

to 2, are obtained by the mild oxidation of the substituted A 501mm of pans of tctfacyalloethykne about mercaptans, i. e., those wherein n=0. The use of equiv- Parts of acetone was Q we bath and alent amounts of hydrogen peroxide or other mild oxidiz- 30 parts of mercaptqacenc and added The l ing agent each Sufide group gives the sulfoxide' The 60 needles were recrystallized from acetone/water solution sulfonyl compounds are obtained when the amount of to give tetrafiyanoethlini' oxidizing agent is increased The new pyrroles of thls invention are useful as inter- Tha new pyrroles of this invention having attached to mediates in the production of pyrrole containing dyes and nuclear carbon two cyano groups and two substituted pigmelits They are useful as mbbflr acceleraftors mercapto groups, such as alkylmercapto or substituted alblswfla hydroxyethylmercapto) dicyanopyr' kyl mercapw groups are Obtained by the tmmmem with role when compounded with polychl orobutadlene accelaqueous solution of a strong mineral acid (pKa of no erated the curing of the latter synthetlc rubber. The sulgrealer than 3) of a 1j4 diamino 2,3 dicyano l,4 bis(sub fonyl and sulfoxy compounds are useful as leather tanstituted-mercapto)butadiene is previously defined. Al-

through dilute acids can be used at elevated temperature, As many apparently Widely different embodiments 0f c. g., up to 100 C., it. is preferred that concentrated acids this invention may be made without departing from the be employed at lower temperatures, preferably 0 to 50 C. Spirit and SCOPE thereof, it i5 0 be d rstood lim t this In addition to hydrochloric acid, sulfuric acid of up to invention is not limited to the specificembodlments' thereof 50% concentration can be used. Other mineral acids except as defined in the appended claims.

such as hydrobromic are useful. The preferred concen- The embodiments of the invention in which an exclu- 7 sive property or privilege is claimed are defined as follows:

i. A compound selected from the class consisting of substituted pyrroles and their alkali metal and ammonium salts, said substituted pyrroles having the structural formula wherein n is a cardinal number from to 2, and R is a radical containing at least one aliphatic carbon and not more than 7 carbon atoms which is bonded to sulfur by aliphatic carbon and is selected from the class consisting of hydrocarbon, hydroxyalkyl, haloalkyl. cyanoalkyl and pyridilium-alkyl radicals.

2. A substituted pyrrole in which each of the nuclear carbon atoms bonded to nuclear nitrogen bears a group wherein R is a hydrocarbon radical containing at least one aliphatic carbon and not more than 7 carbon atoms which is bonded to sulfur by aliphatic carbon and n is cardinal number of 0 to 2, and each of the remaining carbon atoms of the pyrrole nucleus bears a cyano group.

3. A substituted pyrrole in which each of the nuclear carbon atoms bonded to nuclear nitrogen bears a SR group wherein R is an alkyl radical of up to 7 carbon atoms, and each of the remaining carbon atoms of the pyrrole nucleus bears a cyano group.

4. A substituted pyrrole in which each of the nuclear carbon atoms bonded to nuclear nitrogen bears an group wherein R is a hydroxyalkyl radical of up to 7 carbon atoms and n is a cardinal number of 0 to 2, and each of the remaining carbon atoms of the pyrrole nucleus bears a cyano group.

5. A substituted pyrrole in which each of the nuclear carbon atoms bonded to nuclear nitrogen bears an SR group wherein R is a hydroxyalkyl radical of up to 7 carbon atoms, and each of the remaining carbon atoms of the pyrrole nucleus bears a cyano group.

6. A substituted pyrrole in which each of the nuclear carbon atoms bonded to nuclear nitrogen bears an group where R is a chloroalkyl radical of up to 7 carbon atoms, and each of the remaining carbon atoms of the pyrrole nucleus bear a cyano group.

8. A substituted pyrrolide in which each of the nuclear carbon atoms bonded to the nuclear nitrogen bears an group wherein R is a pyridylium-alkyl radical of up to 7 carbon atoms and n is a cardinal number of 0 to 2, and each of the remaining carbon atoms of the pyrrolide nucleus bears a cyano group.

9. 2-,5-bis(methylrnercapto) 3,4 dicyanopyrrole.

til

10. 2,5 bis(beta hydroxyethylmercapto) 3,4 -dicyanopyrrole.

11. 2,5 bis(beta chloroethylsulfonyl) 3,4 dicyanopyrrole.

12. 2,5 bis(2 [l pyridyliumJethylsulfonyl) 3,4- dicyanopyrrolide chloride dihydrate.

13. 2,5 bis(ethylmercapto) 3,4 dicyanopyrrole.

14. Process for preparing substituted pyrroles which comprises contacting an aqueous solution of a strong mineral acid having a pKa of no greater than 3 with a substituted butadiene having the structural formula wherein R is a radical containing at least one aliphatic carbon and not more than 7 carbon atoms which is bonded to sulfur by aliphatic carbon and is selected from the class consisting of hydrocarbon, hydroxyalkyl, haloallcyl, and cyanoalkyl radicals.

15. Process for preparing substituted pyrroles which comprises contacting an aqueous solution of a strong mineral acid having a pKa of no greater than 3 with a substituted butadiene in which each of the central carbon atoms of the butadiene nucleus bears a cyano group and each of the terminal carbon atoms of the butadiene nucleus hear an amino group and a hydroxyalkylmercapto group of not more than 7 carbon atoms.

16. Process for preparing substituted pyrroles which comprises contacting an aqueous solution of a strong mineral acid having a pKa of no greater than 3 and a peroxide with a substituted butadiene in which each of the central carbon atoms of the butadiene nucleus bears a cyano group and each of the terminal carbon atoms of the butadiene nucleus bears an amino group and a hydroxyalkylmercapto group of not more than 7 carbon atoms.

17. Process for preparing substituted pyrroles which comprises contacting an aqueous solution of a strong mineral acid having a pKa of no greater than 3 with a substituted butadiene in which each of the central carbon atoms of the butadiene nucleus bears a cyano group and each of the terminal carbon atoms of the butadiene nucleus bears an amino group and an alkylmercapto group of not more than 7 carbon atoms.

18. Process for preparing 2,5-bis(beta-hydroxyethylmercapto)-3,4-dicyanopyrrole which comprises contact ing an aqueous solution of a strong mineral acid having a pKa of no greater than 3 with l,4-diarnino-l,4-bis (beta hydroxyethylmercapto) 2,3 dicyanobutadiene.

19. Process for preparing 2,5-bis(beta-chloroethylsulfonyl)-3,4-dicyanopyrrole which comprises contacting an aqueous solution of hydrochloric acid and hydrogen peroxide with l,4-diamino-2,3-dicyano-1,4-bis(beta-hydroxycthylmercapto)butadiene.

20. Process for preparing 2,5-bis(methylmercapto)- 3,4-dicyanopyrr0le which comprises contacting an aqueous solution of a strong mineral acid having a pKa of no greater than 3 with 1,4-diamino-l,4-bis(methylmercap to)- 2,3-dicyanobutadiene.

2]. Process for preparing 2,5-bi's(ethylmercapto)-3,4- dicyanopyrrole which comprises contacting an aqueous solution of a strong mineral acid having a pKa of no t greater than 3 with l,4diamino-l,4-bis(ethylmercapto)- 2,3-dicyanobutadiene.

22. Process for preparing 2,5-bis(beta-hydroxyethylmercapto)-3,4-dicyanopyrrole which comprises contacting an aqueous solution of hydrochloric acid with 1,4- diamino-l,4 bis(beta hydroxycthylmercapto) 2,3- dicyanobutadiene.

No references cited. 

1. A COMPOUND SELECTED FROM THE CLASS CONSISTING OF SUBSTITUTED PYRROLES AND THEIR ALKALI METAL AND AMMONIUM SALTS, SAID SUBSTITUTED PYRROLES HAVING THE STRUCTURAL FORMULA 